1. Field of the Invention
The present invention generally relates to an apparatus and method for administering a focused energy treatment to a limited, defined area of a patient's body. The energy treatment is delivered by the use of one or more energy applicators. The energy applicators can be used to release and/or activate thermoactivated drugs and genes for the treatment of both cancerous, precancerous, and benign lesions as well as infectious diseases.
In particular, the present invention relates to a multi-modality treatment employing a localized, focused and regional heating apparatus to treat and/or pretreat a specific body site and to release/activate thermoactivated drugs and genes at the specific body site by using heat. The present invention relates to a heating apparatus and a method of using the same. The apparatus includes one or more energy applicators designed to uniquely provide one or more delivery ports, which deliver the thermoactivated drugs and genes to the specific treatment site. In addition, the applied heat energy may be used to precondition and/or condition the targeted treatment site and also to uniquely cause the fixation and localization of both the release and/or activation of the thermoactivated drugs, genes, or viral vector to the specific treatment site based upon the unique thermo-boundaries formed by the use of heat either before, concurrently, and/or after the delivery of the drug, gene and/or viral vector. As a result, the invention can limit and/or increase the targeted treatment site and minimize the impact on normal cells.
2. Description of the Prior Art
In order to treat a specific treatment site, such as liver lesions, prostate, breast, head and neck, bone, lungs, brain, pancreas, kidney, thyroid or other localized solid or defused neoplasms, doctors have used focused heating devices such as Radio Frequency Ablation (RFA), Microwave Ablation (MA), Laser Ablation (LA), Ultrasound Ablation (UA), High Intensity Focused Ultrasound (HIFU), and focused microwaves (FM) used as a single modality. The previous uses of these treatments were limited in focus and to small effective treatment regions. Recurrent tumors often occur at the margins of a previously treated tumor. There may be ineffective cold spots throughout the treatment zone due to the non-homogeneous nature of these previous heating methods. The use of modalities such as RFA can indeed effectively heat a small defined area of tissue, but this small defined area is limited to tissue in close proximity to a deployed heating antenna. This limited area is usually only within 1 to 2 centimeters of the deployed heating antenna, and this limited area suffers from non-homogeneous heating due to blood flow, tissue impedance, and other types of energy sources. Past uses of prior heat treating apparatuses have resulted in unsatisfactory tumor control, generally limited to the immediate center of the treatment site. As a consequence, significant tumor recurrence and/or continued growth of the cancerous tumors are common. Accordingly, there is a major need to increase the therapeutic kill zone of single heat modalities currently employed.
One of the major uses for the above-described heating devices is for the treatment of hepatocellular carcinoma (HCC). Hepatic tumors are either primary or secondary (i.e. metastatic liver cancer or MLC) and are a substantial medical problem both in the United States and worldwide. The worldwide annual mortality as a result of HCC is estimated annually to be approximately 1,000,000 persons.
Generally, chemotherapy and radiation therapy are ineffective for treatment of hepatic tumors and certain localized tumors where the above heating modalities are used. The gold standard for the treatment of liver tumors and many solid localized tumors is the surgical resection of the tumor. Unfortunately, less than 20% of patients of primary or secondary liver tumors are eligible for surgical resection due to size limitations. This is also the case where solid tumors have advanced in size, such that it may not be safe to remove the tumor from the organ without compromising the well being of the patient. Even with surgical resection, 5 year survival rates are less than 30%. The outlook is even grimmer for patients with unresectable hepatic tumors. Thus, there is a major need for a more effective treatment option for both resectable and unresectable tumors.
Radio-Frequency ablation (RFA) for the treatment of liver cancer was first investigated in the early 1990's. Since that time RFA has quickly become one of the most used minimally invasive treatments for HCC and MLC. There are numerous RFA devices commercially available worldwide to create the thermal lesions that ablate the cancer cells. The three primary RFA devices ultilized in the USA are RITA Medical Systems, Mountain View, Calif.; Radiotherapeutics, Mountain View, Calif.; and Radionics, Burlington, Mass. The power sources of the three devices are very similar in usage, except that the actual RFA heating probes used to deliver heat are different. Both the RITA Medical Systems and the Radiotherapeutics devices have an umbrella or “Christmas tree” configuration while the Radionics device uses a cool tip single or multiple needle design. The RITA Medical Systems device uses a temperature feedback control whereas the other two employ an impedance feedback control to terminate the treatment. The clinical applications placing the RFA probes in the proximity of the tumor can be performed either by open surgery or laproscopically, generally administered by a surgeon, or a less invasive procedure such as percutaneous which is generally administered by interventional radiologists.
However, regardless of which RFA probes are used or which method of clinical application is used, the RFA treatments are best suited for smaller lesions less than 3 cm in diameter. Thus, all of the devices have similar limitations in the ability to effectively treat larger lesions, especially viable cancer cells in the margins. The “margins” are defined by the area outside the solid tumor. The margins outside the boundary area of the tumor in most cases could be up to 2 cm in width. It is desirable to attempt to create tumor free margins or boundaries beyond the imaged tumor lesion of 1 cm or greater; however, RFA is often limited in its ability to produce such consistent margins especially for tumors greater than 3 cm in their maximal diameter. The result is that viable tumor cells are left within such margins or the area between overlapping ablation zones where tissue is heated above 40 degrees C., but temperatures are not achieved within the necessary thermal ablation range (e.g., generally greater than 50 degrees C.).
As a result, known RFA devices are very limited to areas which can be effectively heated to high enough temperatures, generally greater than 50 degrees C. and targeted to be greater than 80 degrees C., in order to ablate the viable cancer. The high temperature requirement presents difficulties in preventing damage to surrounding non-cancerous tissues. Known high temperature ablative devices have had very limited success because it is difficult to heat the cancer cells at the margins to greater than 50 degrees C. to kill the diseased tissue and still prevent significant damage to the surrounding non-cancerous tissue.
High-energy Intensity Focused Ultrasound (HIFU) is another focused heating device. HIFU directs ultrasound to a focused region in order to significantly increase the temperature to kill and/or ablate diseased tissue in the targeted region. HIFU uses ultrasound thousands of times more powerful than the ultrasound used for imaging. Several HIFU systems are clinically available (Ablatherm from EDAP-Technomed, Lyon France and Sonablate from Focus Surgery, Indianapolis, Ind.) as well as several systems under development in China, Europe, and the USA. Treatment applications have included localized prostate cancer, liver cancer, and benign breast and uterine tumors. With regards to the treatment of prostate tumors, these systems may be less invasive than surgery, cyroblation, and seed implants, which have potentially greater adverse events or effects, but the use of HIFU has also been associated with adverse events, such as incontinence, recto-urethral fistulas, edema, and chronic necrotic debris and infection. In addition, due to limitations on the size of treatment zone, the complete control rate will be very difficult to achieve with these known systems. HIFU has also been used for other localized cancers with marginal success due to difficulty of use, limited size of ablation area, and difficulty of focusing and directing the energy to exactly where it is required.
Other technologies, such as lasers as developed by Indigo and Johnson & Johnson, transurethal incision of the prostate (TULIP), and visual laser ablation (VLAP), have similar limitations and clinical shortcomings as those of RFA. These shortcomings include the limited size of the effective targeted area generated by these technologies and potential adverse events caused by the high intensity heat. The inability to see in real time the amount of heat generated and the actual location of where the high heat is generated can also pose a problem and lead to significant cell death in the adjacent normal (healthy) cells. The major shortcomings include not only the non-uniformity within the targeted treatment zone but also the shortcomings of effective heating zones at the margins of the lesions or tumors.
Microwave ablation (MA) probes have been used to deliver heat to lesions or tumors, but this technology is invasive. This technology is very similar to the usage of RFA technologies. To some extent, MA may be limited by the problem of heat sinks around/near blood vessels thereby resulting in cool spots that are not heated to a sufficient temperature to treat and/or kill the lesion or tumor. Another potential limitation is that MA can take longer to heat a very confined area of lesion or tumor tissue.
Drug therapy is a standard of care (SOC) for the treatment of many cancerous and infectious diseases. The goal of drug therapy is to be able to deliver an adequate dose of a drug to the specific organ or site to be treated without damaging or killing normal cells. Cytotoxic drugs for the treatment of disease are generally delivered systemically and thus are non-site specific nor cell-specific. As a result, the delivery of cytotoxic drugs can become very toxic to normal cells and vital organs. Several new drugs have been designed to specifically target the cancer by binding to tumor cell specific antigens. These drugs must typically be very potent to be effective and can kill tumor cells within a specific cancer indication carrying the necessary cell surface receptors. Further, due to physical limitations, blood flow, physiological limitations, higher and more effective doses of anti-cancer agents are generally not achievable. Consequently, for many localized lesions within organs such as the liver, prostate, lung and breast, complete disease site control including the tumor margins has not been significantly improved nor is there a dramatic increase in survival rates.
In some cases, such as with treatment for the prostate gland, the goal is to provide an effective treatment to the diseased region within the gland, without causing major adverse events such as incontinence, sterility, pain, impotency and also retrograde ejaculation. These adverse events are also a byproduct of surgery, external radiation and implant therapy, cyrotherapy, and RFA. Even with thermotherapy, it is necessary to heat a significant portion of the prostate gland while sparing healthy tissues in the prostate as well as the surrounding tissues including the urethral and rectal walls of a patient. Thus, cancer cells in the margins again are not effectively treated. The prostate gland encircles the urethra immediately below the bladder. The prostate, which is the most frequently diseased of all internal organs, not only is a site of a common affliction with cancer among older men, but also for benign prostatic hyperplasia (BPH) and acute prostatitis. Recent treatment of BPH includes transurethral microwave thermotherapy in which microwave energy is employed to elevate the temperature of tissue surrounding the prostatic urethra above about 45° C., thereby thermally damaging the tumorous prostate tissue. U.S. Pat. Nos. 5,330,518 and 5,843,144 describe methods of ablating prostate tumorous tissue by transurethral thermotherapy. There remains a need to better treat diseased tissue to increase the survival rate of patients and decrease the adverse side effects of treatment.